Neurostimulation waveforms having a base component and a high frequency component, and associated systems and methods

ABSTRACT

The present technology provides systems and methods for directly suppressing nerve cells by delivering electrical stimulation having relatively long pulse widths and at amplitudes below an activation threshold of the nerve cells. For example, some embodiments include delivering a therapy signal having individual pulses with pulse widths of between about 5 ms and 100 ms. Directly suppressing the nerve cells is expected to reduce the transmission of pain signals.

CROSS-REFERENCE TO RELATED APPLICATION(S)

The present application claims priority to U.S. Provisional ApplicationNo. 63/209,628, filed Jun. 11, 2021, the disclosure of which isincorporated by reference herein in its entirety.

TECHNICAL FIELD

The present technology is directed towards spinal cord modulation forinhibiting pain, and associated systems and methods.

BACKGROUND

Neurological stimulators have been developed to treat pain, movementdisorders, functional disorders, spasticity, cancer, cardiac disorders,and various other medical conditions. Implantable neurologicalstimulation systems generally have an implantable pulse generator andone or more leads that deliver electrical pulses to neurological tissueor muscle tissue. For example, several neurological stimulation systemsfor spinal cord stimulation (“SCS”) have cylindrical leads that includea lead body with a circular cross-sectional shape and one or moreconductive rings spaced apart from each other at the distal end of thelead body. The conductive rings operate as individual electrodes and, inmany cases, the SCS leads are implanted percutaneously through a needleinserted into the epidural space, with or without the assistance of astylet.

Once implanted, the pulse generator applies electrical pulses to theelectrodes, which in turn modify the function of the patient's nervoussystem, such as by altering the patient's responsiveness to sensorystimuli and/or altering the patient's motor-circuit output. In paintreatment, the pulse generator applies electrical pulses to theelectrodes, which in turn can generate sensations that mask or otherwisealter the patient's sensation of pain. For example, in many cases,patients report a tingling or paresthesia that is perceived as morepleasant and/or less uncomfortable than the underlying pain sensation.While this may be the case for many patients, many other patients mayreport less beneficial effects and/or results. Accordingly, thereremains a need for improved techniques and systems for addressingpatient pain.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1A is a partially schematic illustration of an implantable spinalcord modulation system positioned at a patient's spine to delivertherapeutic signals in accordance with some embodiments of the presenttechnology.

FIG. 1B is a partially schematic, cross-sectional illustration of apatient's spine, illustrating representative locations for implantedlead bodies in accordance with some embodiments of the presenttechnology.

FIG. 2 is a schematic illustration of a representative lead bodysuitable for providing modulation to a patient in accordance withseveral embodiments of the present technology.

FIGS. 3A-3H illustrate representative wave forms associated with therapysignals applied to patients in accordance with particular embodiments ofthe present technology.

FIG. 4 is a flow diagram illustrating a method for treating a patient inaccordance with embodiments of the present technology.

FIG. 5A is a flow diagram illustrating a method for determining amaximum amplitude for a waveform having a given pulse width inaccordance with embodiments of the present technology, and FIG. 5B is aseries of scope traces for determining the maximum amplitude for awaveform having a given pulse width in accordance with the method shownin FIG. 5A.

FIG. 6 is a graph demonstrating the effect of an SCS therapy signalhaving relatively long pulse widths on an animal pain model.

FIGS. 7A-7C are graphs comparing the suppressive effect of several SCStherapy signals on neuron firing rate evoked by nociceptive stimuli.

DETAILED DESCRIPTION

The present technology is generally directed to neurostimulation for thetreatment of pain. In some embodiments, the present technology providestherapy signals having relatively long pulse widths, such as betweenabout 5 ms and about 2 seconds. In some embodiments, the therapy signalsfurther include offset high frequency pulses and/or bursts of highfrequency pulses occurring during the relatively long pulse widths. Forexample, the therapy signal can have a base component having a non-zeroamplitude and a pulse width in a pulse width range of from about 5 msand about 2 second, and a high frequency component including highfrequency pulses having a frequency in a frequency range of from about1.2 kHz to about 100 kHz and occurring from the non-zero amplitude ofthe base component. Without being bound by theory, therapy signals inaccordance with the present technology are expected to advantageouslyaddress one or more physiologic factors contributing to patient pain,such as by directly and/or indirectly suppressing neurons that transmitpain signals to a patient's pain perception centers.

Definitions of selected terms are provided under Heading 1.0(“Definitions”). General aspects of the present technology are describedbelow under Heading 2.0 (“Overview of Present Technology”).Representative treatment systems and their characteristics are describedunder Heading 3.0 (“System Characteristics”) with reference to FIGS. 1A,1B and 2 . Representative methods for treating patients are describedunder Heading 4.0 (“Representative Signals for Directly SuppressingCells”) with reference to FIGS. 3A-4 . Representative results fromanimal studies are described under Heading 5.0 (“Representative Resultsfrom Animal Studies”) with reference to FIGS. 5-6B. Representativeexamples are described under Heading 6.0 (“Representative Examples”).The headings provided herein are for convenience only and do notinterpret the scope or meaning of the claimed present technology.

1.0 Definitions

Unless otherwise stated, the terms “generally,” “about,” and“approximately” refer to values within 10% of a stated value. Forexample, the use of the term “about 100” refers to a range of 90 to 110,inclusive. In instances where relative terminology is used in referenceto something that does not include a numerical value, the terms aregiven their ordinary meaning to one skilled in the art.

As used herein, and unless otherwise noted, the terms “modulate,”“modulation,” “stimulate,” and “stimulation” refer generally to signalsthat have an inhibitory, excitatory, and/or other effect on a targetneural population. Accordingly, a spinal cord “stimulator” can have aninhibitory effect on certain neural populations. Moreover, the use ofthe terms “suppress” and “inhibit” in relation to a therapy signal'seffect on a neuron refers to a reduction in the neuron's firing raterelative to the neuron's baseline firing rate in the absence of thetherapy signal, and does not necessarily refer to a complete eliminationof action potentials in the neuron.

As used herein, “proximate a spinal cord region” refers to the placementof a signal delivery element such that it can deliver electricalstimulation to a neural population associated with the spinal cord orassociated nervous system structures. For example, “proximate a spinalcord region” includes, but is not limited to, the relative leadpositions described and shown in FIG. 1B, as well as other positions notexpressly described herein.

As used herein, the term “pulse width” refers to the width of any phaseof a repeating pulse, such as the portion of a pulse at a givenpolarity, unless explicitly described otherwise. For example, the use ofthe term pulse width with respect to a signal having bi-phasic pulsescan refer to the duration of an anodic pulse phase or a cathodic pulsephase. The use of the term pulse width with respect to a signal havingmonophasic pulses can refer to the duration of the monophasic pulsephase.

2.0 Overview of the Present Technology

The present technology is directed generally to spinal cord modulationand associated systems and methods for treating pain. In someembodiments, representative techniques include applying a therapy signalhaving a relatively long pulse width of about 5 ms to about 2 seconds toa spinal cord region of a patient. In some embodiments, the therapysignals further include offset high frequency pulses and/or bursts ofhigh frequency pulses occurring during the relatively long pulse widths.The therapy signal can be applied at an amplitude that is below theactivation threshold of neurons adjacent the signal delivery element.Without being bound by theory, the use of therapy signals in accordancewith the present technology is expected to advantageously address one ormore physiologic factors contributing to patient pain, such as bydirectly and/or indirectly suppressing neurons that transmit painsignals to a patient's pain perception centers. Therapy signals appliedin accordance with the present technology are expected to reduce varioustypes of pain, including but not limited to chronic low back pain (e.g.,neuropathic pain, and/or nociceptive pain, and/or other types of pain,depending upon the patient) and/or chronic leg pain.

The present technology represents a departure from conventional SCS.Conventional SCS systems were originally derived from the gate controltheory of pain, which suggested that the activity of large diametersensory fiber systems could influence small diameter pain fibertransmission to the higher neural centers where the pain signals resultin the conscious perception of pain. The interaction between the largediameter and small diameter neurons was thought to be mediated byinhibitory interneurons in the dorsal horn. Exciting these inhibitoryinterneurons was thought to have a suppressing influence on ‘widedynamic range’ (WDR) neurons, which are considered the main output forpain of the spinal gate. The early clinical targets for stimulationincluded the dorsal columns, which are the central primary afferentpathway for innocuous sensations from large sensory fibers. This“conventional” stimulation required the patient experience paresthesia,but resulted in reasonable pain relief for a large number of patientsover decades.

During the last two decades, mechanistic studies began to highlight theidea that SCS was not stopping small fiber transmission (the ‘drive’behind nociceptive pain), but rather was treating central sensitization.Central sensitization is the amplification of pain circuits, forexample, in the dorsal horn. In particular, central sensitization canmanifest as (1) an increase in sensitivity of WDR neurons to afferentinput (resulting in hyperalgesia, allodynia, etc.); (2) activity of theWDR neurons in the absence of afferent input (resulting in spontaneous,ongoing pain); and/or (3) concomitant hypersensitization of nominal‘nociceptive-specific’ (NS) projection neurons (also resulting inhyperalgesia). It is believed that paresthesia-based SCS inhibitedspontaneous WDR neuron activity very indirectly. Stimulating the dorsalcolumns would provide an epiphenomenon of paresthesia, but would alsosend signals into the spinal gate. These signals entering the gate woulddrive the inhibitory interneurons, which then could inhibit the WDRneurons. To achieve inhibition of the WDR neurons, both (i) the correctdorsal column fibers had to be stimulated and (ii) the inhibitoryinterneurons had to provide the key link between the dorsal columnfibers and the hyperactive WDR neurons. If the correct dorsal columnfibers could not be activated (for example, if they were too deep in thespinal cord, if the lead position was not optimal, etc.), or if theinhibitory interneurons were not adequate for the task (e.g., if therewere too few inhibitory interneurons to inhibit the WDR neurons), painrelief could not be achieved.

High Frequency SCS (e.g., stimulation at a frequency greater than about1.2 kHz) allowed for superior pain relief in more patients thanconventional stimulation, particularly in patients with neuropathic backpain. Mechanistic studies of high frequency SCS, in general agreementwith clinical data, have shown that the inhibitory interneurons can bedirectly driven by the stimulation field, without the need to activatedorsal column fibers. Additionally, mechanistic studies of 10 kHzlow-intensity SCS have shown that both WDR and NS neurons can beinhibited. Because it is believed that high frequency SCS may bypass thestep of activating the dorsal columns, high frequency SCS may enable agreater degree of flexibility for lead placement and does not requirethat the patient experience paresthesia. Indeed, theclinically-effective stimulation amplitudes of 10 kHz SCS are below thedorsal column threshold.

The present technology, however, includes signals that are expected todirectly suppress target neurons in the superficial dorsal horn paincircuits (e.g., the NS and WDR neurons) in lieu of and/or in addition tosuppressing neurons via other mechanisms. For example, as described ingreater detail below, signals having a pulse width between about 5 msand about 2 seconds can electrically mediate the function of the targetneurons to directly suppress the target neurons. Without intending to bebound by theory, the signals having a pulse width between about 5 ms andabout 2 seconds may cause neural membrane channels of the target neuronsto enter a net inactivate state that prevents the neurons from firing.This is in contrast to conventional SCS and high frequency SCS, both ofwhich indirectly mediate the NS and/or WDR neurons by inducing releaseof neurotransmitter from an upstream neuron (e.g., dorsal column fibersand/or inhibitory interneurons), that may have an inhibitory effect onthe downstream target neuron. Without being bound by theory, it isexpected that directly targeting the NS and WDR neurons bypasses theneed to activate the inhibitory interneurons to achieve a reduction inpain transmission. Accordingly, the present technology provides therapysignals and associated systems and methods that directly suppress atleast a subset of target neurons, such as NS and WDR neurons, to providepain relief. The present technology further provides therapy signalsthat incorporate both a high frequency component and a base componenthaving a pulse width between about 5 ms and about 2 seconds such thatthe signal may address pain through multiple mechanisms of action and/ora combination of the previously described mechanisms of action (e.g.,direct suppression as a result of the base component and inhibitoryinterneuron activation by the high frequency component). As demonstratedbelow, this combination may provide superior pain relief relative toexisting therapy signals in at least some patients.

Specific details of certain embodiments of the disclosure are describedbelow with reference to methods for modulating one or more target neuralpopulations (e.g., nerves) or sites of a patient, and associatedimplantable structures for providing the modulation. Although selectedembodiments are described below with reference to modulating the dorsalcolumn, dorsal horn, dorsal root, dorsal root entry zone, and/or otherparticular regions of the spinal column to control pain, the modulationmay in some instances be directed to other neurological structuresand/or target neural populations of the spinal cord and/or otherneurological tissues. Some embodiments can have configurations,components or procedures different than those described in this section,and other embodiments may eliminate particular components or procedures.A person of ordinary skill in the relevant art, therefore, willunderstand that the present disclosure may include other embodimentswith additional elements, and/or may include other embodiments withoutseveral of the features shown and described below with reference toFIGS. 1A-4 .

3.0 System Characteristics

FIG. 1A schematically illustrates a representative patient therapysystem 100 for treating a patient's motor and/or other functioning,arranged relative to the general anatomy of the patient's spinal column191. The system 100 can include a signal generator 101 (e.g., animplanted or implantable pulse generator or IPG), which may be implantedsubcutaneously within a patient 190 and coupled to one or more signaldelivery elements or devices 110. The signal delivery elements ordevices 110 may be implanted within the patient 190, at or off thepatient's spinal cord midline 189. The signal delivery elements 110carry features for delivering therapy to the patient 190 afterimplantation. The signal generator 101 can be connected directly to thesignal delivery devices 110, or it can be coupled to the signal deliverydevices 110 via a signal link, e.g., a lead extension 102. In someembodiments, the signal delivery devices 110 can include one or moreelongated lead(s) or lead body or bodies 111 (identified individually asa first lead 111 a and a second lead 111 b). As used herein, the termssignal delivery device, signal delivery element, lead, and/or lead bodyinclude any of a number of suitable substrates and/or supporting membersthat carry electrodes/devices for providing therapy signals to thepatient 190. For example, the lead or leads 111 can include one or moreelectrodes or electrical contacts that direct electrical signals intothe patient's tissue, e.g., to provide for therapeutic relief. In someembodiments, the signal delivery elements 110 can include structuresother than a lead body (e.g., a paddle) that also direct electricalsignals and/or other types of signals to the patient 190, e.g., asdisclosed in U.S. Patent Application Publication No. 2018/0256892,incorporated herein by reference in its entirety. For example, paddlesmay be more suitable for patients with spinal cord injuries that resultin scarring or other tissue damage that impedes cylindrical leads.

In some embodiments, one signal delivery device may be implanted on oneside of the spinal cord midline 189, and a second signal delivery devicemay be implanted on the other side of the spinal cord midline 189. Forexample, the first and second leads 111 a, 111 b shown in FIG. 1A may bepositioned just off the spinal cord midline 189 (e.g., about 1 mmoffset) in opposing lateral directions so that the two leads 111 a, 111b are spaced apart from each other by about 2 mm. In some embodiments,the leads 111 may be implanted at a vertebral level ranging from, forexample, about T4 to about T12. In some embodiments, one or more signaldelivery devices can be implanted at other vertebral levels, e.g., asdisclosed in U.S. Pat. No. 9,327,121, incorporated herein by referencein its entirety.

The signal generator 101 can transmit signals (e.g., electrical signals)to the signal delivery elements 110 that excite and/or suppress targetnerves. The signal generator 101 can include a machine-readable (e.g.,computer-readable or controller-readable) medium containing instructionsfor generating and transmitting suitable therapy signals, such as thosedescribed below with respect to FIGS. 3A-3D. The signal generator 101and/or other elements of the system 100 can include one or moreprocessor(s) 107, memory unit(s) 108, and/or input/output device(s) 112.Accordingly, the process of providing modulation signals, providingguidance information for positioning the signal delivery devices 110,establishing battery charging and/or discharging parameters, and/orexecuting other associated functions can be performed bycomputer-executable instructions contained by, on, or incomputer-readable media located at the pulse generator 101 and/or othersystem components. Further, the pulse generator 101 and/or other systemcomponents may include dedicated hardware, firmware, and/or software forexecuting computer-executable instructions that, when executed, performany one or more methods, processes, and/or sub-processes described inthe materials incorporated herein by reference. The dedicated hardware,firmware, and/or software also serve as “means for” performing themethods, processes, and/or sub-processes described herein. The signalgenerator 101 can also include multiple portions, elements, and/orsubsystems (e.g., for directing signals in accordance with multiplesignal delivery parameters), carried in a single housing, as shown inFIG. 1A, or in multiple housings. For example, the signal generator caninclude some components that are implanted (e.g., a circuit that directssignals to the signal delivery device 110), and some that are not (e.g.,a power source). The computer-executable instructions can be containedon one or more media that are implanted within the patient and/orpositioned external to the patient, depending on the embodiment.

The signal generator 101 can also receive and respond to an input signalreceived from one or more sources. The input signals can direct orinfluence the manner in which the therapy, charging, and/or processinstructions are selected, executed, updated, and/or otherwiseperformed. The input signals can be received from one or more sensors(e.g., an input device 112 shown schematically in FIG. 1A for purposesof illustration) that are carried by the signal generator 101 and/ordistributed outside the signal generator 101 (e.g., at other patientlocations) while still communicating with the signal generator 101. Thesensors and/or other input devices 112 can provide inputs that depend onor reflect patient state (e.g., patient position, patient posture,and/or patient activity level), and/or inputs that arepatient-independent (e.g., time). Still further details are included inU.S. Pat. No. 8,355,797, incorporated herein by reference in itsentirety.

In some embodiments, the signal generator 101 and/or signal deliverydevices 110 can obtain power to generate the therapy signals from anexternal power source 103. For example, the external power source 103can by-pass an implanted signal generator and generate a therapy signaldirectly at the signal delivery devices 110 (or via signal relaycomponents). The external power source 103 can transmit power to theimplanted signal generator 101 and/or directly to the signal deliverydevices 110 using electromagnetic induction (e.g., RF signals). Forexample, the external power source 103 can include an external coil 104that communicates with a corresponding internal coil (not shown) withinthe implantable signal generator 101, signal delivery devices 110,and/or a power relay component (not shown). The external power source103 can be portable for ease of use.

In some embodiments, the signal generator 101 can obtain the power togenerate therapy signals from an internal power source, in addition toor in lieu of the external power source 103. For example, the implantedsignal generator 101 can include a non-rechargeable battery or arechargeable battery to provide such power. When the internal powersource includes a rechargeable battery, the external power source 103can be used to recharge the battery. The external power source 103 canin turn be recharged from a suitable power source (e.g., conventionalwall power).

During at least some procedures, an external stimulator or trialmodulator 105 can be coupled to the signal delivery elements 110 duringan initial procedure, prior to implanting the signal generator 101. Forexample, a practitioner (e.g., a physician and/or a companyrepresentative) can use the trial modulator 105 to vary the modulationparameters provided to the signal delivery elements 110 in real time,and select optimal or particularly efficacious parameters. Theseparameters can include the location from which the electrical signalsare emitted, as well as the characteristics of the electrical signalsprovided to the signal delivery devices 110. In some embodiments, inputis collected via the external stimulator or trial modulator 105 and canbe used by the clinician to help determine what parameters to vary. In atypical process, the practitioner uses a cable assembly 120 totemporarily connect the trial modulator 105 to the signal deliverydevice 110. The practitioner can test the efficacy of the signaldelivery devices 110 in an initial position. The practitioner can thendisconnect the cable assembly 120 (e.g., at a connector 122), repositionthe signal delivery devices 110, and reapply the electrical signals.This process can be performed iteratively until the practitioner obtainsthe desired position for the signal delivery devices 110. Optionally,the practitioner may move the partially implanted signal deliverydevices 110 without disconnecting the cable assembly 120. Furthermore,in some embodiments, the iterative process of repositioning the signaldelivery devices 110 and/or varying the therapy parameters may not beperformed.

The signal generator 101, the lead extension 102, the trial modulator105 and/or the connector 122 can each include a receiving element 109.Accordingly, the receiving elements 109 can be patient implantableelements, or the receiving elements 109 can be integral with an externalpatient treatment element, device or component (e.g., the trialmodulator 105 and/or the connector 122). The receiving elements 109 canbe configured to facilitate a simple coupling and decoupling procedurebetween the signal delivery devices 110, the lead extension 102, thepulse generator 101, the trial modulator 105 and/or the connector 122.The receiving elements 109 can be at least generally similar instructure and function to those described in U.S. Patent ApplicationPublication No. 2011/0071593, incorporated by reference herein in itsentirety.

After the signal delivery elements 110 are implanted, the patient 190can receive therapy via signals generated by the trial modulator 105,generally for a limited period of time. During this time, the patientwears the cable assembly 120 and the trial modulator 105 outside thebody. Assuming the trial therapy is effective or shows the promise ofbeing effective, the practitioner then replaces the trial modulator 105with the implanted signal generator 101, and programs the signalgenerator 101 with therapy programs selected based on the experiencegained during the trial period. Optionally, the practitioner can alsoreplace the signal delivery elements 110. In still further embodiments,the signal generator 101 can be implanted without first undergoing atrial period. Once the implantable signal generator 101 has beenpositioned within the patient 190, the therapy programs provided by thesignal generator 101 can still be updated remotely via a wirelessphysician's programmer 117 (e.g., a physician's laptop, a physician'sremote or remote device, etc.) and/or a wireless patient programmer 106(e.g., a patient's laptop, patient's remote or remote device, etc.).Generally, the patient 190 has control over fewer parameters than doesthe practitioner. For example, the capability of the patient programmer106 may be limited to starting and/or stopping the signal generator 101,and/or adjusting the signal amplitude within a present amplitude range.The patient programmer 106 may be configured to accept inputscorresponding to pain relief, motor functioning and/or other variables,such as medication use. Accordingly, more generally, embodiments of thepresent technology include receiving patient feedback, via a sensor,that is indicative of, or otherwise corresponds to, the patient'sresponse to the signal. Feedback includes, but is not limited to, motor,sensory, and verbal feedback. In response to the patient feedback, oneor more signal parameters can be adjusted, such as frequency, pulsewidth, amplitude, or delivery location.

FIG. 1B is a cross-sectional illustration of the spinal cord 191 and anadjacent vertebra 195 (based generally on information from Crossman andNeary, “Neuroanatomy,” 1995 (published by Churchill Livingstone)), alongwith multiple leads 111 (shown as leads 111 a-111 e) implanted atrepresentative locations. For purposes of illustration, multiple leads111 are shown in FIG. 1B implanted in a single patient. In addition, forpurposes of illustration, the leads 111 are shown as elongated leadshowever, leads 111 can be paddle leads. In actual use, any given patientwill likely receive fewer than all the leads 111 shown in FIG. 1B.

The spinal cord 191 is situated within a vertebral foramen 188, betweena ventrally located ventral body 196 and a dorsally located transverseprocess 198 and spinous process 197. Arrows V and D identify the ventraland dorsal directions, respectively. The spinal cord 191 itself islocated within the dura mater 199, which also surrounds portions of thenerves exiting the spinal cord 191, including the ventral roots 192,dorsal roots 193, and dorsal root ganglia 194. The dorsal roots 193enter the spinal cord 191 at the dorsal root entry region 187, andcommunicate with dorsal horn neurons located at the dorsal horn 186. Insome embodiments, the first and second leads 111 a, 111 b are positionedjust off the spinal cord midline 189 (e.g., about 1 mm offset) inopposing lateral directions so that the two leads 111 a, 111 b arespaced apart from each other by about 2 mm, as discussed above. In someembodiments, a lead or pairs of leads can be positioned at otherlocations, e.g., toward the outer edge of the dorsal root entry portion187 as shown by a third lead 111 c, or at the dorsal root ganglia 194,as shown by a fourth lead 111 d, or approximately at the spinal cordmidline 189, as shown by a fifth lead 111 e.

In some embodiments the devices and systems of the present technologyinclude features other than those described herein. For example, onelead 111 to six leads 111 can be positioned generally end-to-end at ornear the patient's midline M and span vertebral levels from about T4 toabout T12. In some embodiments, two, three, or four leads 111 arepositioned end-to-end at or near the patient's midline from T4 to T12.In some embodiments, the leads 111 and/or other signal delivery devicescan have locations other than those expressly shown herein. For example,one or more signal delivery devices can be positioned at the dorsal sideof the spinal cord 191. In addition, the devices and systems of thepresent technology can include more than one internal stimulator and/ormore than one external stimulator that can be configured for wirelessstimulation, such as by using electromagnetic waves.

Several aspects of the technology are embodied in computing devices,e.g., programmed/programmable pulse generators, controllers and/or otherdevices. The computing devices on/in which the described technology canbe implemented may include one or more central processing units, memory,input devices (e.g., input ports), output devices (e.g., displaydevices), storage devices, and network devices (e.g., networkinterfaces). The memory and storage devices are computer-readable mediathat may store instructions that implement the technology. In someembodiments, the computer readable media are tangible media. In someembodiments, the data structures and message structures may be stored ortransmitted via an intangible data transmission medium, such as a signalon a communications link. Various suitable communications links may beused, including but not limited to a local area network and/or awide-area network.

FIG. 2 is a partially schematic illustration of a representative leadbody 111 that may be used to apply modulation to a patient in accordancewith any of the foregoing embodiments. In general, the lead body 111includes a multitude of electrodes or contacts 120. When the lead body111 has a circular cross-sectional shape, as shown in FIG. 2 , thecontacts 120 can have a generally ring-type shape and can be spacedapart axially along the length of the lead body 111. In a particularembodiment, the lead body 111 can include eight contacts 120, identifiedindividually as first, second, third . . . eighth contacts 121, 122, 123. . . 128. In general, one or more of the contacts 120 are used toprovide signals, and another one or more of the contacts 120 provide asignal return path. Accordingly, the lead body 111 can be used todeliver monopolar modulation (e.g., if the return contact is spacedapart significantly from the delivery contact), or bipolar modulation(e.g., if the return contact is positioned close to the delivery contactand in particular, at the same target neural population as the deliverycontact). In still further embodiments, the pulse generator 101 (FIG.1A) can operate as a return contact for monopolar modulation.

4.0 Representative Signals

FIG. 3A is a partially schematic illustration of a representativetherapy signal 300 a used to delivery therapy in accordance withembodiments of the present technology. The therapy signal 300 a includesbiphasic pulses 301 a repeating in a continuous manner. Each individualpulse 301 a includes an anodic pulse phase 302 a, a cathodic pulse phase304 a, and an interphase interval 306 a separating the anodic pulsephase 302 a and the cathodic pulse phase 304 a. In the illustratedembodiment, the anodic pulse phase 302 a and the cathodic pulse phase304 a are symmetrical (e.g., having generally equal pulse widths andgenerally equal and opposite amplitudes) such that individual pulses 301a are charge balanced. Individual pulses 301 a are separated by aninterpulse interval 308 a. Together, the pulse 301 a and the interpulseinterval 308 a define a pulse period 310 a. The pulse period 310 arepeats in cycles that define a frequency of the therapy signal 300 a.

The therapy signal 300 a can have relatively long pulse widths, such asbetween about 5 ms and about 2 seconds. Accordingly, the anodic pulsephase 302 a and the cathodic pulse phase 304 a can each have a pulsewidth in a range of from about 5 ms to about 2 seconds. In embodimentsfor which the pulse 301 a is a monophasic pulse, the monophasic pulsephase can have a pulse width between about 5 ms to about 2 seconds, orbetween about 5 ms and about 1 second, or between about 100 ms and about1 second, or between about 100 ms and about 500 ms. Representative pulsewidths include about 5 ms, about 10 ms, about 25 ms, about 50 ms, about75 ms, about 100 ms, about 200 ms, about 300 ms, about 400 ms, about 500ms, about 600 ms, about 700 ms, about 800 ms, about 900 ms, about 1second, and/or about 2 seconds. In some embodiments, the pulse width isgreater than about 5 ms, greater than about 10 ms, greater than about 25ms, greater than about 50 ms, greater than about 75 ms, greater thanabout 100 ms, greater than about 500 ms, and/or greater than about 1second. In the illustrated embodiment, the anodic pulse phase 302 a andthe cathodic pulse phase 304 a have generally equal pulse widths thatcan offset charge build up in a signal delivery element (e.g.,electrodes 120) and/or surrounding tissue. In other embodiments, and asdescribed below with respect to FIG. 3B, the anodic pulse phase andcathodic pulse phase do not have the same pulse width. In yet otherembodiments, the stimulation charge recovery is a passive process, inwhich a shunt resistance is connected across the active electrodes toallow for charge built up on the output and Helmholtz capacitances fromthe therapeutic pulse (e.g., the anodic pulse phase 302 a) to ‘bleedoff’. In such embodiments, the therapy signal may be essentially amonophasic signal. As one skilled in the art will recognize, thefrequency of the therapy signal 300 a is based at least in part on thepulse width of the pulses 301 a. For example, pulses with longer pulsewidths typically (but not always) have lower frequencies. Accordingly,in some embodiments the frequency of the therapy signal 300 a is lessthan about 100 Hz, less than about 10 Hz, less than about 5 Hz, and/orless than about 1 Hz.

The pulses 301 a can have an amplitude (e.g., current amplitude orvoltage amplitude) below the activation threshold of a target neuronalpopulation. In such embodiments, the therapy signal 300 a does notinduce an action potential in target neurons when it is delivered to thetarget neuronal population. Generally, the activation of neurons dependson two variables: the strength (e.g., amplitude) of the signal and theduration (e.g., pulse width) for which the signal is applied. As theduration of the signal increases, the amplitude required to induceneuronal activation decreases. Accordingly, the amplitude of the pulses301 a is inversely related to the pulse width of the pulses 301 a. Insome embodiments, the amplitude remains below the rheobase of the targetneuronal population. The rheobase refers to the minimum amplitude thatresults in neuronal activation when the therapy signal is applied for acontinuous period (e.g., a period exceeding 100 ms, 200 ms, 300 ms,etc.). In some embodiments, the rheobase can be approximated bymeasuring the amplitude at which a patient exhibits the first clinicallydiscernable effects of the signal. For example, in some embodiments, theamplitude of the pulses 301 a is about 3 mA or less, such as betweenabout 0.1 mA and about 2.5 mA or between about 0.5 mA and about 2 mA.

Use of relatively long pulse widths such as those described for thesignal 300 a shown in FIG. 3A can cause substantial charge to build upin the electrodes delivering the signal. Therefore, the pulse width andthe amplitude of the pulse 301 a can also be selected to remain below anacceptable charge and/or charge density for the electrode materials usedto deliver the therapy signal 300 a. As one skilled in the art willappreciate, exceeding the acceptable or “maximum” charge and/or chargedensity of the electrodes may cause electrolysis on the surface of theelectrode, distort the therapy signal delivered by the electrode,increase corrosion of the electrode, shorten the expected lifespan ofthe electrode, and/or cause the electrode to emit materials or productsthat can damage the surrounding tissue. Accordingly, the pulse width andamplitude of the pulse 301 a can be selected to deliver atherapeutically effective charge to the target neural population withoutcausing one or more of the foregoing events associated with exceeding amaximum charge density of the electrode. Suitable electrode materialsinclude platinum (e.g., platinum iridium) and other materials and alloysknown in the art. For platinum electrodes, the pulse width and/oramplitude can be selected such that the charge density remains at orbelow about 300 μC/cm², which is currently a clinically acceptablemaximum charge density for platinum electrodes. Table 1 below providesamplitude values that, for a set of particular pulse widths, generate acharge density of approximately 300 μC/cm² on a typical neurostimulationlead with electrodes of geometric surface area of approximately 12.7mm².

TABLE 1 Signal Parameters for 300 μC/cm² Charge Density on an Electrodewith Geometric Surface Area of 12.7 mm² Pulse Width (ms) Amplitude (mA)10 3.81 30 1.27 100 0.38 300 0.13 1000 0.04

The amplitude values in Table 1 are normalized to produce a 300 μC/cm²charge density at the recited pulse widths. The recited amplitude valuestherefore represent the “maximum” amplitude that, for the recited pulsewidths, do not exceed the 300 μC/cm² charge density threshold. Inembodiments in which the upper charge density threshold is a value otherthan 300 μC/cm², the corresponding amplitude values would change as well(assuming pulse width stays the same). For example, if the upper chargedensity threshold was greater than 300 μC/cm², the associated amplitudevalues would increase as well. In some embodiments, such as thosedescribed below with respect to FIGS. 5A and 5B, the maximum amplitudeand/or upper charge density threshold that can be accommodated beforeinducing an event associated with exceeding a maximum charge densitythreshold for an electrode (e.g., waveform distortion, electrode surfacebubbling, etc.) can be determined and used as the maximum amplitudeand/or charge density threshold during waveform parameter selection.

In some embodiments, the pulse width and/or amplitude are selected suchthat the charge density approaches the maximum charge density permittedby the electrode material (e.g., within 5% of the maximum chargedensity, within 10% of the maximum charge density, within 20% of themaximum charge density, etc.). As described below, and without beingbound by theory, applying the therapy signal 300 a at an amplitude thatis below the activation threshold of a target neuronal population but atan amplitude and pulse width combination that delivers relatively highcharge densities is expected to directly suppress at least a subset ofthe target neuronal population. Because the native charge densities ofpolished electrodes can deliver sufficient charge over the relativelylong pulse widths described herein, the electrodes do not necessarilyrequire a coating material. However, in some embodiments, the electrodesnevertheless include a coating material (e.g., to increase the electrodesurface area). The number of electrodes programmed to deliver the signalcan also affect the total maximum charge. For example, in someembodiments, three electrodes are programmed as anodic and threeelectrodes are programmed as cathodic such that the total charge beingdelivered to the target neural population can be increased withoutexceeding the maximum charge density for any individual electrode.

In some embodiments, systems in accordance with the present technologyinclude an algorithm that limits the stimulation charge to be below theacceptable charge and charge density for the electrode materials. Beforedelivering the therapy signal 300 a, a user can input electrodeinformation into a patient treatment system component (e.g., a graphicaluser interface on a modulator, controller, programmer, or other suitabledevice). In some embodiments, the electrode information is alreadystored in the patient treatment system, and/or the patient treatmentsystem automatically calculates some or all of the electrodeinformation. The electrode information can contain the electrodematerial, the surface area of the electrodes, and/or the number ofelectrodes (e.g., the number of anodes and the number of cathodes). Insome embodiments, the surface area of the electrodes can be estimatedfrom an impedance value associated with the electrode, which may beautomatically detected by the system. For example, lower impedancevalues are associated with higher electrode surface areas. The user canthen select a desired pulse width from a list or range of availablepulse widths (e.g., between 5 ms and 2 seconds). Based at least in parton the selected pulse width and the electrode information, the algorithmcan determine the upper limit of the programmable amplitude (e.g., the“maximum amplitude”) based upon a calculation of maximum allowed chargedensity. For example, if a user inputs and/or the system determines thatthe electrodes are polished platinum iridium electrodes, the electrodeshave a specific impedance value and/or surface area, and the pulse widthis 30 ms, the algorithm can calculate the maximum amplitude that can beused without exceeding a charge density of 300 μC/cm2, which asreflected in Table 1 is about 1.27 mA.

In some embodiments, the maximum amplitude is below an activationthreshold of a target neuronal population for the selected pulse width.For example, the maximum amplitude can be set below the rheobase of thefirst clinically discernable effect of the stimulation. As described ingreater detail with respect to FIG. 4 , the activation may be determinedor approximated by slowly increasing the stimulation amplitude at a setpulse width (e.g., 5 ms) and asking the patient to report any sensory orphysical perceptions from the stimulation. If the activation thresholdhas an amplitude value less than the maximum amplitude based on thecharge density calculation, the activation threshold amplitude value canbe entered into the patient treatment system (e.g., via the interface onthe modulator, controller, or programmer) to set a new maximum amplitudefor the therapy signal 300 a.

FIG. 3B is a partially schematic illustration of another representativetherapy signal 300 b. Certain aspects of therapy signal 300 b aregenerally similar to those described above with respect to the therapysignal 300 a shown in FIG. 3A. For example, therapy signal 300 bincludes a pulse period 310 b having a biphasic pulse 301 b and aninterpulse interval 308 b. The pulse 301 b has an anodic pulse phase 302b and a cathodic pulse phase 304 b separated by an interphase interval306 b. Unlike the therapy signal 300 a shown in FIG. 3A, however, thepulses 301 b shown in FIG. 3B do not have symmetrical anodic pulsephases 302 b and cathodic pulse phases 304 b. Rather, the cathodic pulsephase 304 b has a shorter pulse width and a greater amplitude than theanodic pulse phase 302 b. In other embodiments, therapy signal 300 b canhave an anodic pulse phase 302 b that has a shorter pulse width and agreater amplitude than the cathodic pulse phase 304 b (e.g., a mirrorimage of therapy signal 300 b). Regardless, the pulse width andamplitude of the cathodic pulse phase 304 b can nevertheless be selectedsuch that the total charge delivered in the anodic pulse phase 302 b andthe cathodic pulse phase 304 b remains substantially equal to avoidhaving a charge build up in the electrode or the patient's tissue. Insome embodiments, the amplitude of the anodic pulse phase 302 b canremain below the activation threshold that results in the firstclinically discernable effect of the stimulation (and/or below therheobase). Similarly, the larger amplitude of the cathodic pulse phase302 b also remains below the threshold of a clinically discernableeffect of stimulation (and/or below the rheobase). One expectedadvantage of therapy signal 300 b is the recovery period takes lesstime, meaning the duration between subsequent anodic pulse phases 302 bis less and the frequency of the pulse period 310 b can be higher.

FIG. 3C illustrates a representative therapy signal 300 c with a rampingperiod 312. The ramping period 312 transitions between a maximumamplitude of the anodic pulse phase 302 c and a maximum amplitude of thecathodic pulse phase 304 c. In some embodiments (e.g., as describedbelow with respect to FIG. 3E), the anodic pulse phase 302 c and thecathodic pulse phase 304 c can include a portion of the ramping period312. The ramping period 312 can have a duration that is substantiallyequal to the pulse width of the therapy signal 300 c. For example, ifthe anodic pulse phase 302 c and the cathodic pulse phase 304 c eachhave a pulse width of about 100 ms, the ramping period 312 can have aduration of about 100 ms. Accordingly, the ramping period 312 can have aduration between about 5 ms and about 2 seconds. In other embodiments,the ramping period 312 is less than or greater than the pulse width ofthe anodic pulse phase 302 c and/or the cathodic pulse phase 304 c.Although the anodic pulse phase 302 c and the cathodic pulse phase 304 care illustrated as symmetrical, the anodic pulse phase 302 c and thecathodic pulse phase 304 c can also have a configuration similar to thatdescribed above with respect to FIG. 3B, with the ramping period 312extending therebetween.

FIG. 3D illustrates another therapy signal 300 d having a non-continuousramping period 312 between the anodic pulse phase 302 d and the cathodicpulse phase 304 d during pulse period 310 d. The noncontinuous rampingperiod can include a first ramping period 312 a immediately followingthe anodic pulse phase 302 d and the cathodic pulse phase 304 d, and asecond ramping period 312 b immediately preceding the anodic pulse phase302 d and the cathodic pulse phase 304 d. The first ramping period 312 aand the second ramping period 312 b can be separated by an interphaseinterval 306 d (e.g., between an anodic pulse phase 302 d and cathodicpulse phase 304 d within the same pulse 301 d) or an interpulse interval308 d (e.g., between adjacent pulses 301 d). The first ramping period312 a and the second ramping period 312 b can have the same or differentdurations. Together, the first ramping period 312 a and the secondramping period 312 b can have a duration substantially equal to thepulse width of the therapy signal 301 d (e.g., between about 5 ms andabout 2 seconds). In other embodiments, the first ramping period 312 aand the second ramping period 312 b together have a duration that isless than or greater than the pulse width of the therapy signal 301 d.

As indicated above, some embodiments of the present technology includetherapy signals having ramped, or at least partially ramped, anodicpulse phases and/or ramped, or at least partially ramped, cathodic pulsephases. For example, FIG. 3E illustrates a representative ramped therapysignal 300 e in which the therapy signal 300 e includes an anodic pulsephase 302 e having a first ramping period 312 a and a second rampingperiod 312 b, and a cathodic pulse phase 304 e having a third rampingperiod 312 c and a fourth ramping period 312 d. As described above, theanodic pulse phase 302 e may have a pulse width of between about 5 msand about 2 seconds, and the cathodic pulse phase 304 e may have a pulsewidth of between about 5 ms and about 2 seconds. The second rampingperiod 312 b can immediately follow the first ramping period 312 a, asillustrated in FIG. 3E, or the second ramping period 312 b can be spacedapart from the first ramping period 312 a by a period of the anodicpulse phase 302 a having a constant amplitude (e.g., as illustrated inFIG. 3C). Likewise, the fourth ramping period 312 d can immediatelyfollow the third ramping period 312 c, as also illustrated in FIG. 3E,or the fourth ramping period 312 d can be spaced apart from the thirdramping period 312 c by a period of the cathodic pulse phase 304 ahaving a constant amplitude (e.g., as illustrated in FIG. 3C). In theillustrated embodiment, the second ramping phase 312 b of the anodicpulse phase 302 e immediately transitions into the third ramping period312 c of the cathodic pulse phase 304 e. However, in other embodimentsthe second ramping period 312 b of the anodic pulse phase 302 e can beseparated from the third ramping period 312 c of the cathodic pulsephase 304 e by an interphase interval (e.g., as illustrated in FIG. 3D).In the illustrated embodiment, the pulse period 310 e is equal to theduration of the pulse 301 e. However, in other embodiments respectivepulses 301 e can be separated by an interpulse interval (e.g., thefourth ramping period 312 d can be separated from the first rampingperiod 312 a).

FIG. 3F illustrates another representative therapy signal 300 f used todeliver therapy in accordance with embodiments of the presenttechnology. Unlike the therapy signals 300 a-300 e of FIGS. 3A-3E, whichhave a square wave form, a ramped wave form, or a combination thereof,the therapy signal 300 f of FIG. 3F has a sinusoidal wave form pattern(or other non-linear pattern) comprising repeating curved pulses 301 f.Each individual pulse 301 f has an anodic pulse phase 302 f and acathodic pulse phase 304 f. Similar to the signals 300 a-300 e describedabove, the anodic pulse phase 302 f may have a pulse width between about5 ms and about 2 seconds, and the cathodic pulse phase 304 f may have apulse width between about 5 ms and about 2 seconds.

Each of therapy signals 300 a-f is expected to globally or at leastpartially suppress target neurons (e.g., NS and WDR neurons in thesuperficial dorsal horn pain circuits) when delivered to a patient'sspinal cord region. As described above, suppressing the target neuronsis expected to inhibit or otherwise reduce the transmission of painsignals to the brain. In some embodiments, the therapy signals 300 a-fare expected to preferentially suppress hyperactive neurons, such asthose that may be responsible for a patient's pain.

Any of the signals 300 a-f described above may further include offsethigh frequency pulses and/or bursts of high frequency pulses occurringduring the anodic and/or cathodic pulse phases (e.g., pulses startingand ending at the non-zero amplitudes of the anodic and cathodic pulsephases). For example, FIG. 3G illustrates a representative signal 300 gthat is generally similar to the therapy signal 300 a shown in FIG. 3Abut further includes high frequency pulses 316 g occurring during theanodic pulse phase 302 g and the cathodic pulse phase 304 g of the pulse301 g. As illustrated, the high frequency pulses 316 g generally occurduring the anodic pulse phase 302 g and/or the cathodic pulse phase 304g, but are generally absent during the interphase interval 306 g and theinterpulse interval 308 g. Although shown as occurring during both theanodic pulse phase 302 g and the cathodic pulse phase 304 g, in otherembodiments, the high frequency pulses 316 g occur only during theanodic pulse phase 302 g. In yet other embodiments, the high frequencypulses 316 g occur only during the cathodic pulse phase 304 g.

The high frequency pulses 316 g can have a frequency in a frequencyrange of from about 1.2 kHz and about 100 kHz. For example, the highfrequency pulses 316 g can have a frequency in a frequency range of fromabout 1.2 kHz to about 50 kHz, from about 1.2 kHz to about 25 kHz, fromabout 3 kHz to about 15 kHz, or from about 5 kHz to about 15 kHz. Insome embodiments, the high frequency pulses 316 g have a frequency ofabout 5 kHz, about 10 kHz, about 15 kHz, about 20 kHz, about 25 kHz,about 50 kHz, or about 100 kHz. The high frequency pulses 316 g can havea pulse width in a pulse width range of from about 10 microseconds toabout 333 microseconds, from about 25 microseconds to about 166microseconds, from about 33 microseconds to about 100 microseconds, orfrom about 50 microseconds to about 166 microseconds. In someembodiments, such as the embodiment illustrated in FIG. 3G, the highfrequency pulses 316 g have an amplitude that is greater than theamplitude of the underlying anodic pulse phase 302 g and/or the cathodicpulse phase 304 g. In other embodiments, the high frequency pulses 316 ghave an amplitude that is equal to or less than the amplitude of theanodic pulse phase 302 g and/or the cathodic pulse phase 304 g. Furtheryet, although shown as bi-phasic pulses, the high frequency pulses 316 gmay instead be monophasic pulses. The high frequency pulses 316 g canalso have a ramped and/or sinusoidal shape.

The anodic pulse phase 302 g may have an overall pulse width betweenabout 5 ms and about 2 seconds (not accounting for any phase changeduring the high frequency pulses 316 g), as described in detail abovefor the signal 300 a of FIG. 3A. Likewise, the cathodic pulse phase 304g may also have an overall pulse width between about 5 ms and about 2seconds (not accounting for any phase change during the high frequencypulses 316 g).

The therapy signal 300 g can be described as having a base component(e.g., base component pulses or low frequency pulses having the anodicpulse phase 302 g and the cathodic pulse phase 304 g) and a highfrequency component (e.g., the high frequency pulses 316 g). The basecomponent may also be referred to as a low frequency component. In someembodiments, the base component and the high frequency component are asingle waveform, and therefore are generally administered using the sameelectrodes/contacts. In other embodiments, the high frequency componentis superimposed over the base component to create the therapy signal 300g.

FIG. 3H illustrates another representative signal 300 h used to delivertherapy in accordance with embodiments of the present technology. Thesignal 300 h is generally similar to the signal 300 g shown in FIG. 3G,but instead of delivering high frequency pulses during the entirety of(or at least approximately the entirety of) the anodic pulse phase andthe cathodic pulse phase, the signal 300 h includes high frequency pulsebursts 314 h (“the bursts 314 h”) occurring during only portions of theanodic pulse phase 302 h and the cathodic pulse phase 304 h of the pulse301 h. Sequential bursts 314 h are separated by a quiescent period 318h. As illustrated, the bursts 314 h generally occur during the anodicpulse phase 302 h and/or the cathodic pulse phase 304 h, but aregenerally absent during the interphase interval 306 h and the interpulseinterval 308 h. Although shown as occurring during both the anodic pulsephase 302 h and the cathodic pulse phase 304 h, in other embodiments,the bursts 314 h occur only during the anodic pulse phase 302 h. In yetother embodiments, the bursts 314 h occur only during the cathodic pulsephase 304 h.

The bursts 314 h include one or more individual high frequency pulses316 h repeating at an intra-burst frequency in a frequency range of fromabout 1.2 kHz and about 100 kHz, from about 1.2 kHz to about 50 kHz,from about 1.2 kHz to about 25 kHz, from about 3 kHz to about 15 kHz, orfrom about 5 kHz to about 15 kHz. In some embodiments, the intra-burstfrequency of the high frequency pulses 316 h is about 5 kHz, about 10kHz, about 15 kHz, about 20 kHz, about 25 kHz, about 50 kHz, or about100 kHz. The high frequency pulses 316 h can have a pulse width in apulse width range of from about 10 microseconds to about 333microseconds, from about 25 microseconds to about 166 microseconds, fromabout 33 microseconds to about 100 microseconds, or from about 50microseconds to about 166 microseconds. In some embodiments, such as theembodiment illustrated in FIG. 3H, the high frequency pulses 316 h havean amplitude that is greater than the amplitude of the underlying anodicpulse phase 302 h and/or the cathodic pulse phase 304 h. In otherembodiments, the high frequency pulses 316 h have an amplitude that isequal to or less than the amplitude of the anodic pulse phase 302 hand/or the cathodic pulse phase 304 h. Further yet, although shown asbi-phasic pulses, the high frequency pulses 316 h may instead bemonophasic pulses. The high frequency pulses 316 h can also have aramped and/or sinusoidal shape.

Each sequential burst of the high frequency pulse bursts 314 h caninclude the same or a different number of individual high frequencypulses 316 h, compared to the preceding burst 314 h. For example, in theillustrated embodiment, the bursts 314 h are shown as having eithereight or four individual high frequency pulses 316 h. In otherembodiments, other numbers of high frequency pulses 316 h can bedelivered during the bursts 314 h.

The anodic pulse phase 302 h may have an overall pulse width betweenabout 5 ms and about 2 seconds (not accounting for any phase changeduring the bursts 314 h), as described in detail above for the signal300 a of FIG. 3A. Likewise, the cathodic pulse phase 304 h may also havean overall pulse width between about 5 ms and about 2 seconds (notaccounting for any phase change during the bursts 314 h).

As with the therapy signal 300 g of FIG. 3G, the therapy signal 300 h ofFIG. 3H can also be described as having a base component (e.g., theanodic pulse phase 302 h and the cathodic pulse phase 304 h) and a highfrequency component (e.g., burst 314 h of high frequency pulses 316 h).In some embodiments, the base component and the high frequency componentare a single waveform. In other embodiments, the high frequencycomponent is superimposed over the base component to create the therapysignal 300 h.

FIG. 4 is a block diagram illustrating a method 400 for treating apatient in accordance with embodiments of the present technology. Someor all of the steps in the method 400 can be performed by a processorexecuting instructions stored on or more elements of a patient treatmentsystem. The method 400 can include receiving a first input includingelectrode information (step 402). The electrode information can relateto certain characteristics of one or more electrodes of the patienttreatment system that are implanted in, or implantable into, the patientfor delivering an electrical signal to a target neural population. Inparticular, the electrode information can include, among other things,the electrode material, the surface area of the electrode, and/or thenumber of electrodes. In addition to or in lieu of the surface area, theelectrode information can include impedance values associated with theone or more electrodes. If impedance values are received, the method 400can optionally include calculating the surface area based at least inpart on the impedance values. The first input can be received from auser inputting the electrode information into a graphical user interfaceor other suitable means included as part of the patient treatmentsystem, such as a modulator, controller, programmer, or other suitabledevice. In some embodiments, the first input can be received byaccessing a memory storing the electrode information. In addition, oneor more of the foregoing inputs can be received/retrieved from acomputer-readable storage medium, and/or otherwise generated without adirect user input.

The method 400 can continue by receiving a second input corresponding toa desired pulse width (step 404). The second input can also be receivedfrom a user inputting the electrode information into the graphical userinterface or other suitable device. In some embodiments, the graphicaluser interface can include a list of available pulse widths (e.g.,ranging from 5 ms to 2 seconds) and the input corresponds to a userselecting one of the available pulse widths. In other embodiments, theuser can directly input a desired pulse width without selecting from alist of available pulse widths. In yet other embodiments, the patienttreatment system may automatically select or recommend a pulse width.

Based at least in part on the electrode information and the pulse width,the processor can calculate a maximum amplitude that can be deliveredwithout exceeding the maximum charge density of the electrodes and/orinducing events associated with exceeding the maximum charge density ofthe electrodes (e.g., using the algorithm described above with respectto FIG. 3A) (step 406). In some embodiments, the maximum amplitude canbe determined by testing the waveform having the selected pulse width atincremental amplitudes until an event associated with exceeding themaximum charge density of the electrodes is observed, as described laterwith respect to FIGS. 5A and 5B. The maximum amplitude may also be setto avoid exciting the target neuronal tissue (e.g., the maximumamplitude can be below an activation threshold of the neurons). Todetermine the maximum amplitude that avoids exciting the target neuronaltissue, a signal with the selected pulse width can be delivered to thepatient via the electrodes, and the amplitude can be increased (e.g.,incrementally or continuously) until either (i) the maximum amplitudebased on the charge density calculation is reached, or (ii) a clinicallydiscernable effect other than the therapeutic effect of the therapysignal is observed in the patient. If the maximum amplitude based on thecharge density calculation is reached before a clinically discernableeffect other than the therapeutic effect of the therapy signal isobserved, the maximum amplitude remains unchanged. If, however, theamplitude at which the clinically discernable effect is observed is lessthan the maximum amplitude based on the charge density calculation, theamplitude at which the clinically discernable effect is observed can beset as the new maximum amplitude. In other embodiments, the amplitude atwhich the clinically discernable effect is observed can be determinedbefore calculating the maximum amplitude based on the charge densitycalculation.

The method 400 can continue by directing a therapy signal having thepulse width and an amplitude less than or equal to the maximum amplitudeto the target neural population (step 408). For example, the modulator,controller, or programmer can direct a pulse generator to generate thetherapy signal and deliver, via the electrodes, the therapy signal tothe target neural population. Without being bound by theory, the therapysignal directly suppresses the target neurons to reduce the patient'spain.

Other suitable methods for delivering the therapy signals describedherein can also be used. In some embodiments, the steps of receiving theelectrode information and determining a maximum amplitude based on themaximum charge density can be omitted. In such embodiments, a pulsewidth is selected and various amplitudes are tested to determine amaximum amplitude beyond which the patient begins to exhibit aclinically discernable effect. The signal can then be applied at anamplitude less than the determined maximum amplitude. The therapysignals described herein can also be applied in combination with othertherapies, such as high frequency SCS or conventional SCS.

As indicated above, the present technology further includes techniquesfor determining a maximum amplitude that can be delivered at a givenpulse width. For example, FIG. 5A is a flowchart of a method 500 fordetermining a maximum amplitude at which a waveform having a given pulsewidth can be administered, without distorting the waveform. The methodcan begin in step 502 by recording the voltage potential of an electrodeoutputting a waveform having a given pulse width at a plurality ofincremental amplitudes. This may include selecting a pulse width (e.g.,10 microseconds, 30 microseconds, 100 microseconds, 300 microseconds,1,000 microseconds, etc.) and recording a trace (e.g., a measurement ofthe electrode voltage over time, as might be observed on an oscilloscopetrace) of the waveform having the selected pulse width at the pluralityof incremental amplitudes. The increment may include a stepwiseincrement, with each subsequent amplitude increasing by a common amount(e.g., 100 μA) relative to a preceding amplitude. In other embodiments,the increment between subsequent amplitudes may be variable. FIG. 5Bprovides an example of a plurality of voltage potential traces recordedusing a voltage measurement system (in this case, an oscilloscope) for awaveform having a pulse width of 300 microseconds. The scope traces wererecorded at incremental amplitudes of 50 μA, 100 μA, 150 μA, 200 μA, 300μA, 400 μA, 500 μA, 750 μA, and 1,000 μA. In some embodiments, thevoltage can be measured at step 502 on the surface of the electrodebeing tested, via another electrode positioned adjacent the electrodebeing tested, via a register connected in series between a pulsegenerator and the electrode being tested, or another suitable recordingtechnique.

Returning to FIG. 5A, the method 500 can continue in step 504 bydetermining, based on the recordings taken in step 502, the amplitude atwhich the waveform begins to distort. This may include, for example,manually or automatically analyzing the morphology of the voltagepotential or other recordings measured in step 502 to identify waveformdistortion. In some embodiments, waveform distortion may present as areversal or inflection in the slope of the waveform in the voltagepotential as the voltage potential increases (e.g., which may bereferred to as a “shoulder”). The amplitude at which the shoulder orinflection appears is therefore the amplitude at which waveformdistortion begins. In FIG. 5B, for example, the shoulder (identified bythe arrows marked “x”) is first observed in the voltage potential traceof the waveform at an amplitude of 200 μA. In some embodiments,determining the amplitude at which the waveform distorts can includeidentifying a reversal or inflection in the slope that exceeds a minimumthreshold to account for any potential noise in the signal.

The method 500 can continue in step 506 by determining (e.g., selecting)the maximum amplitude for the waveform based at least in part on thedetermination made in step 504. For example, the maximum amplitude canbe set as the largest tested amplitude that does not induce waveformdistortion. In FIG. 5B, for example, the largest tested amplitude atwhich waveform distortion does not occur is 150 μA. Thus, 150 μA couldbe selected as the maximum amplitude. Optionally, determining themaximum amplitude can include testing a plurality of additionalincremental amplitudes between the amplitude determined in step 504 andthe amplitude determined in step 506 to further “fine tune” the maximumamplitude. For example, in the embodiment shown in FIG. 5B, steps 502,504, and 506 could be repeated for a plurality of incremental amplitudesbetween 150 μA and 200 μA.

Once the maximum amplitude is determined in step 506, the method 500 canoptionally continue in step 508 by calculating the maximum chargedensity based on the maximum amplitude determined in step 504. This maybe done by multiplying the pulse width and the amplitude to obtain thecharge per phase of the waveform, and then dividing the charge per phaseby the electrode surface area.

For patient safety, steps 502-506 of the method 500 are generallyperformed with the electrode in a saline bath or other suitableenvironment rather than with the electrode implanted in a patient.However, once the maximum amplitude is determined in step 506 and/or themaximum charge density is determined in step 508, the method 500 cancontinue in step 510 by programming a signal generator to deliver atherapy signal having an amplitude less than or equal to the maximumamplitude to a target neural population in a patient's spinal cordregion.

Of note, waveform distortion is often the first adverse effect ofexceeding a maximum charge density threshold of an electrode. Thus,while other adverse effects (e.g., electrode bubbling, electrodecorrosion, etc.) can occur if the maximum charge density is exceeded,such events usually occur at amplitudes that are greater than theamplitude at which waveform distortion occurs. Thus, using waveformdistortion to set the maximum amplitude threshold is also expected toprevent the other adverse effects identified herein that are associatedwith exceeding a maximum charge density of an electrode.

5.0 Representative Results from Animal Studies

The assignee of the present application, Nevro Corp., has conductedpreliminary animal studies to demonstrate the effect of therapy signalshaving relatively long pulse widths, such as those described herein. Ina first study, the effectiveness of a signal having relative long pulsewidths was tested on rats with surgically-induced allodynia. Inparticular, two rats underwent spinal nerve ligation (SNL) to inducemechanical sensitivity (allodynia) in the rats. The effect of SCS usingtherapy signals with relatively long pulse widths was then assessedusing von Frey (vF) paw withdrawal testing, as compared to (a) pre-SNLvF testing, and (b) post-SNL vF testing during periods without SCSapplication. The SCS was applied as a 0.5 kHz sine wave (i.e., theanodic pulse phase had a pulse width of 1 second and the cathodic pulsephase had a pulse width of 1 second) with a 150-200 μA fixed amplitude.FIG. 6 is a graph depicting the behavioral response (i.e. paw withdrawalthreshold) of the rats to the vF testing. As shown, the paw withdrawalthreshold decreased approximately 20% as a result of the SNL surgery,but was restored by about half during application of SCS. This indicatesthat SCS with relatively long pulse widths reduced the allodynia in therats.

In another animal study, three different SCS therapy signals were testedto determine the impact of the therapy signals on theelectrophysiological response of rat spinal neurons to increasingnociceptive vF stimuli. The first therapy signal was a bi-phasic signalhaving an anodic phase pulse width of 1 second, a cathodic phase pulsewidth of 1 second, and an amplitude of 150-200 μA (e.g., generallysimilar to the therapy signal 300 a shown in FIG. 3A), the secondtherapy signal was a high frequency bi-phasic signal having a frequencyof 10 kHz, and the third therapy signal was a bi-phasic signal having ananodic phase pulse width of 300 ms, a cathodic phase pulse width of 300ms, and offset 10 kHz high frequency pulses occurring during the anodicand cathodic pulse phases (e.g., generally similar to the therapy signal300 g described with respect to FIG. 3A). Nociceptive vF stimuli ofincreasing intensity were administered to the rats during application ofthe first signal, the second signal, the third signal, and in theabsence of any SCS signal. The neuron firing rate evoked in response tothe nociceptive vF stimuli was then measured.

FIG. 7A depicts the neuron firing rate evoked in ten different neuronsof a first animal in response to the vF stimuli during application ofthe first signal, the second signal, and in the absence of any SCSsignal. More specifically, FIG. 7A includes a first graph 700 aillustrating the neuronal firing rate evoked by vF stimuli of variousintensities in the absence of any SCS, a second graph 700 b illustratingthe neuronal firing rate evoked by vF stimuli of various intensitiesduring application of the first signal (shown as S1 in FIG. 7A), and athird graph 700 c illustrating the neuronal firing rate evoked by vFstimuli of various intensities during application of the second signal(shown as S2 in FIG. 7A). The evoked neuronal responses shown in thegraphs 700 a-c are determined as the difference between the neuronalactivity immediately following application of the vF stimulus and theneuronal activity immediately preceding application of the vF stimulus,with each line representing an individual neuron's response. A “flatter”line therefore represents a relatively smaller increase in evokedresponse as the vF stimulus intensity is increased, whereas a “steeper”line represents a larger increase in evoked response as the vF stimulusintensity is increased. Although one neuron appeared to be more activethan the others, the general response of the neurons to stimuli ofincreasing intensity can be observed from graphs 700 a-700 c. Asillustrated, both the second graph 700 b and the third graph 700 c showa generally flatter evoked neural response (compared to the first graph700 a) as the vF stimuli was increased in intensity. Accordingly, boththe first signal S1 and the second signal S2 partially suppressed theneuronal firing evoked by the nociceptive vF stimulus (e.g., each signalat last partially suppressed the neurons) relative to the neuronalfiring evoked in the absence of SCS.

FIG. 7B depicts the neuron firing rate evoked in six different neuronsof a second animal in response to the vF stimuli during application ofthe third signal and in the absence of any SCS signal. Morespecifically, FIG. 7B includes a fourth graph 700 d illustrating theneuronal firing rate evoked by vF stimuli of various intensities in theabsence of any SCS and a fifth graph 700 e illustrating the neuronalfiring rate evoked by vF stimuli of various intensities duringapplication of the third signal (shown as S3 in FIG. 7B). The responsein the fourth graph 700 d is different than the response in the firstgraph 700 a of FIG. 7A because the results shown in FIG. 7B wereobtained using a different animal (and thus a different set of neurons)than the results shown in FIG. 7A. However, as with the graphs of FIG.7A, the evoked neuronal responses shown in the graphs 700 d and 700 eare determined as the difference between the neuronal activityimmediately following application of the vF stimulus and the neuronalactivity immediately preceding application of the vF stimulus, with eachline representing an individual neuron's response. As shown by thefourth graph 700 d, in the absence of any SCS signal the evoked responseto the vF stimuli generally increased as the intensity of the vF stimuliwas increased. Of note, the fifth graph 700 e shows a generally flatterevoked neural response (compared to the fourth graph 700 d) as the vFstimuli was increased in intensity. Accordingly, the third signal S3partially suppressed the neuronal firing evoked by the nociceptive vFstimulus (e.g., the third signal S3 at least partially suppressed theneurons) relative to the neuronal firing rate evoked in the absence ofSCS.

FIG. 7C is a graph showing the change in slope between the neuralresponse evoked by the vF stimuli during application of SCS and theneural response evoked by the vF stimuli during periods of no SCSapplication. For the first signal S1, this includes the change in theaverage slope of the lines shown in graph 700 b relative to the averageslope of the lines shown in graph 700 a of FIG. 7A. For the secondsignal S2, this includes the change in the average slope of the linesshown in the graph 700 c relative to the average slope of the linesshown in the graph 700 a of FIG. 7A. For the third signal S3, thisincludes the change in the average slope of the lines shown in graph 700e relative to the average slope of the lines shown in the graph 700 d ofFIG. 7B. In particular, a larger decrease in slope corresponds to agreater degree of neural suppression relative to the baseline.

As illustrated in FIGS. 7A-7C, the first therapy signal S1, the secondtherapy signal S2, and the third therapy signal S3 each significantlyreduced the neuron firing evoked by the nociceptive vF stimulus. None ofthe therapy signals reduced neuron firing rate by a statisticallysignificant amount relative to the other therapy signals, although thethird signal S3 did tend to show, on average, a larger reduction inneuron firing than the first therapy signal S1 and the second therapysignal S2. Moreover, because these studies are preliminary, thereduction in firing rates achieved by administering the first signal S1and the third signal S3, both of which have a relatively long pulsewidth in accordance with the present technology, is expected to increaseas the amplitudes and other parameters for these signals are optimized.Also, due to the heterogeneity of nervous tissue and patientpopulations, the first signal S1 and/or the third signal S3 may producea greater neural suppression for certain neurons and/or in certainpatient populations.

6.0 Representative Examples

The following examples are provided to further illustrate embodiments ofthe present technology and are not to be interpreted as limiting thescope of the present technology. To the extent that certain embodimentsor features thereof are mentioned, it is merely for purposes ofillustration and, unless otherwise specified, is not intended to limitthe present technology. It will be understood that many variations canbe made in the procedures described herein while still remaining withinthe bounds of the present technology. Such variations are intended to beincluded within the scope of the presently disclosed technology.

1. A patient treatment system, comprising:

-   -   a signal generator having a computer readable storage medium        with instructions that, in operation, generate a therapy signal        having a base component and a high frequency component, wherein—        -   the base component has pulses with a non-zero amplitude and            a pulse width in a pulse width range of from about 5 ms to            about 2 seconds, and        -   the high frequency component includes high frequency pulses            having a frequency in a frequency range of from about 1.2            kHz and about 100 kHz, wherein the high frequency pulses            have an origin at the non-zero amplitude of the base            component; and    -   a signal delivery element coupleable to the signal generator,        wherein the signal delivery element is positionable proximate a        spinal cord region, and, in operation, delivers the therapy        signal to the spinal cord region.

2. The patient treatment system of example 1 wherein the pulse width ofthe base component pulses is in a pulse width range of from about 5 msto about 100 ms.

3. The patient treatment system of examples 1 or 2 wherein the pulsewidth of the base component pulses is in a pulse width range of fromabout 50 ms to about 2 seconds.

4. The patient treatment system of any of examples 1-3 wherein the pulsewidth of the base component pulses is in a pulse width range of fromabout 100 ms to about 2 seconds.

5. The patient treatment system of any of examples 1-4 wherein the pulsewidth of the base component pulses is in a pulse width range of fromabout 500 ms to about 2 seconds.

6. The patient treatment system of any of examples 1-5 wherein the highfrequency pulses have an amplitude greater than the non-zero amplitudeof the base component pulses.

7. The patient treatment system of any of examples 1-6 wherein the highfrequency pulses have a frequency of 10 kHz.

8. The patient treatment system of any of examples 1-7 wherein the highfrequency pulses have a pulse width in a pulse width range of betweenabout 10 microseconds and about 333 microseconds.

9. The patient treatment system of any of examples 1-8 wherein the highfrequency pulses include bursts of high frequency pulses, whereinadjacent bursts of high frequency pulses are separated by a quiescentinterval during which no high frequency pulses are delivered.

10. The patient treatment system of any of examples 1-9 wherein the basecomponent pulses include a plurality of biphasic pulses having an anodicpulse phase and a cathodic pulse phase, and wherein at least one of theanodic pulse phase or the cathodic pulse phase has the pulse width inthe pulse width range from about 5 ms to about 2 seconds.

11. The patient treatment system of example 10 wherein the highfrequency pulses occur during the anodic pulse phase and/or the cathodicpulse phase.

12. The patient treatment system of examples 10 or 11 wherein the basecomponent pulses include an interphase interval between the anodic pulsephase and the cathodic pulse phase, and wherein the high frequencypulses do not occur during the interphase interval.

13. The patient treatment system of any of examples 10-12 whereinadjacent bi-phasic pulses of the plurality of biphasic pulses of thebase component pulses are separated by an interpulse interval, andwherein the high frequency pulses do not occur during the interpulseinterval.

14. The patient treatment system of any of examples 10-13 wherein thehigh frequency pulses include bursts of high frequency pulses, whereinadjacent bursts of high frequency pulses are separated by a quiescentinterval during which no high frequency pulses are delivered.

15. The patient treatment system of example 14 wherein at least twobursts of high frequency pulses occur during each anodic pulse phaseand/or each cathodic pulse phase.

16. The patient treatment system of any of examples 1-9 wherein the basecomponent pulses include a plurality of monophasic pulses having thenon-zero amplitude.

17. The patient treatment system of any of examples 1-16 wherein thetherapy signal at least partially suppresses at least a subset ofneurons in the spinal cord region.

18. The patient treatment system of example 17 wherein the subset ofneurons includes WDR neurons.

19. The patient treatment system of example 17 wherein the subset ofneurons includes NS neurons.

20. The patient treatment system of example 17 wherein the subset ofneurons includes both WDR neurons and NS neurons.

21. The patient treatment system of any of examples 1-20 wherein thesignal delivery element includes an electrode, and wherein the non-zeroamplitude of the base component pulses is selected to be at or below amaximum amplitude of the therapy signal that the electrode can toleratebased at least in part on the pulse width, the electrode material,and/or the surface area of the electrode.

22. A method for treating a patient, comprising:

-   -   programming a signal generator to deliver a therapy signal to a        target neural population in the patient's spinal cord region via        at least one implanted signal delivery element, wherein the        therapy signal includes (i) a base component having pulses with        a non-zero amplitude and a pulse width in a pulse width range of        from about 5 ms to about 2 seconds, and (ii) a high frequency        component including high frequency pulses having a frequency in        a frequency range of from about 1.2 kHz and about 100 kHz,        wherein the high frequency pulses have an origin at the non-zero        amplitude of the base component.

23. The method of example 22 wherein the pulse width of the basecomponent pulses is in a pulse width range of from about 5 ms to about100 ms.

24. The method of examples 22 or 23 wherein the pulse width of the basecomponent pulses is in a pulse width range of from about 50 ms to about2 seconds.

25. The method of any of examples 22-24 wherein the pulse width of thebase component pulses is in a pulse width range of from about 100 ms toabout 2 seconds.

26. The method of any of examples 22-25 wherein the pulse width of thebase component pulses is in a pulse width range of from about 500 ms toabout 2 seconds.

27. The method of any of examples 22-26 wherein the high frequencypulses have an amplitude greater than the non-zero amplitude of the basecomponent pulses.

28. The method of any of examples 22-27 wherein the high frequencypulses have a frequency of 10 kHz.

29. The method of any of examples 22-28 wherein the high frequencypulses have a pulse width in a pulse width range of between about 10microseconds and about 333 microseconds.

30. The method of any of examples 22-29 wherein the high frequencypulses include bursts of high frequency pulses, wherein adjacent burstsof high frequency pulses are separated by a quiescent interval duringwhich no high frequency pulses are delivered.

31. The method of any of examples 22-30 wherein the base componentpulses include a plurality of biphasic pulses having an anodic pulsephase and a cathodic pulse phase, and wherein at least one of the anodicpulse phase or the cathodic pulse phase has the pulse width in the pulsewidth range from about 5 ms to about 2 seconds.

32. The method of example 31 wherein the high frequency pulses occurduring the anodic pulse phase and/or the cathodic pulse phase.

33. The method of examples 31 or 32 wherein the base component pulsesinclude an interphase interval between the anodic pulse phase and thecathodic pulse phase, and wherein the high frequency pulses do not occurduring the interphase interval.

34. The method of any of examples 31-33 wherein adjacent bi-phasicpulses of the plurality of biphasic pulses of the base component pulsesare separated by an interpulse interval, and wherein the high frequencypulses do not occur during the interpulse interval.

35. The method of any of examples 31-34 wherein the high frequencypulses include bursts of high frequency pulses, wherein adjacent burstsof high frequency pulses are separated by a quiescent interval duringwhich no high frequency pulses are delivered.

36. The method of example 35 wherein at least two bursts of highfrequency pulses occur during each anodic pulse phase and/or eachcathodic pulse phase.

37. The method of any of examples 22-30 wherein the base componentpulses include a plurality of monophasic pulses having the non-zeroamplitude.

38. The method of any of examples 22-37 wherein the therapy signal atleast partially suppresses at least a subset of neurons in the spinalcord region.

39. The method of example 38 wherein the subset of neurons includes WDRneurons.

40. The method of example 38 wherein the subset of neurons includes NSneurons.

41. The method of example 38 wherein the subset of neurons includes bothWDR neurons and NS neurons.

42. The method of any of examples 22-41 wherein the signal deliveryelement includes an electrode, and wherein the non-zero amplitude of thebase component pulses is at or below a maximum amplitude of the therapysignal that the electrode can tolerate based at least in part on thepulse width, the electrode material, and/or the surface area of theelectrode.

43. A method for treating a patient, comprising:

-   -   applying a therapy signal to the patient via a treatment system,        wherein the treatment system includes a signal delivery element        positioned proximate a spinal cord region of the patient, and        wherein the therapy signal includes (i) a base component having        pulses with a non-zero amplitude and a pulse width in a pulse        width range of from about 5 ms to about 2 seconds, and (ii) a        high frequency component including high frequency pulses having        a frequency in a frequency range of from about 1.2 kHz and about        100 kHz, wherein the high frequency pulses have an origin at the        non-zero amplitude of the base component.

44. The method of example 43 wherein the pulse width of the basecomponent pulses is in a pulse width range of from about 5 ms to about100 ms.

45. The method of examples 43 or 44 wherein the pulse width of the basecomponent pulses is in a pulse width range of from about 50 ms to about2 seconds.

46. The method of any of examples 43-45 wherein the pulse width of thebase component pulses is in a pulse width range of from about 100 ms toabout 2 seconds.

47. The method of any of examples 43-46 wherein the pulse width of thebase component pulses is in a pulse width range of from about 500 ms toabout 2 seconds.

48. The method of any of examples 43-47 wherein the high frequencypulses have an amplitude greater than the non-zero amplitude of the basecomponent pulses.

49. The method of any of examples 43-48 wherein the high frequencypulses have a frequency of 10 kHz.

50. The method of any of examples 43-49 wherein the high frequencypulses have a pulse width in a pulse width range of between about 10microseconds and about 333 microseconds.

51. The method of any of examples 43-50 wherein the high frequencypulses includes bursts of high frequency pulses, wherein adjacent burstsof high frequency pulses are separated by a quiescent interval duringwhich no high frequency pulses are delivered.

52. The method of any of examples 43-51 wherein the base componentpulses include a plurality of biphasic pulses having an anodic pulsephase and a cathodic pulse phase, and wherein at least one of the anodicpulse phase or the cathodic pulse phase has the pulse width in the pulsewidth range from about 5 ms to about 2 seconds.

53. The method of example 52 wherein the high frequency pulses occurduring the anodic pulse phase and/or the cathodic pulse phase.

54. The method of examples 52 or 53 wherein the base component pulsesinclude an interphase interval between the anodic pulse phase and thecathodic pulse phase, and wherein the high frequency pulses do not occurduring the interphase interval.

55. The method of any of examples 52-54 wherein adjacent bi-phasicpulses of the plurality of biphasic pulses of the base component pulsesare separated by an interpulse interval, and wherein the high frequencypulses do not occur during the interpulse interval.

56. The method of any of examples 52-55 wherein the high frequencypulses include bursts of high frequency pulses, wherein adjacent burstsof high frequency pulses are separated by a quiescent interval duringwhich no high frequency pulses are delivered.

57. The method of example 56 wherein at least two bursts of highfrequency pulses occur during each anodic pulse phase and/or eachcathodic pulse phase.

58. The method of any of examples 43-51 wherein the base componentpulses include a plurality of monophasic pulses having the non-zeroamplitude.

59. The method of any of examples 43-58 wherein the therapy signal atleast partially suppresses at least a subset of neurons in the spinalcord region.

60. The method of example 59 wherein the subset of neurons includes WDRneurons.

61. The method of example 59 wherein the subset of neurons includes NSneurons.

62. The method of example 59 wherein the subset of neurons includes bothWDR neurons and NS neurons.

63. The method of any of examples 43-62 wherein the signal deliveryelement includes an electrode, and wherein the non-zero amplitude of thebase component pulses is at or below a maximum amplitude of the therapysignal that the electrode can tolerate based at least in part on thepulse width, the electrode material, and/or the surface area of theelectrode.

64. A method for determining a maximum amplitude for a therapy signalhaving a pulse width, the method comprising:

-   -   recording, at a plurality of incremental amplitudes, an        electrode voltage potential for the therapy signal having the        pulse width;    -   based on the recording, determining a distortion amplitude of        the plurality of incremental amplitudes at which the therapy        signal begins to distort; and    -   based at least in part on the distortion amplitude, determining        the maximum amplitude for the therapy signal.

65. The method of example 64 wherein recording an electrode voltagepotential for the therapy signal at the plurality of incrementalamplitudes includes recording the trace of the electrode voltagepotential at each of the plurality of incremental amplitudes.

66. The method of example 65 wherein determining a distortion amplitudeincludes analyzing a morphology of the electrode potential traces toidentify a waveform distortion feature.

67. The method of any of examples 64-66, further comprising calculatinga maximum charge density based at least in part on the set pulse widthand the maximum amplitude.

68. The method of any of examples 64-67, further comprising programminga signal generator to deliver a therapy signal to a target neuralpopulation in a patient's spinal cord region, wherein the therapy signalhas an amplitude less than or equal to the maximum amplitude.

7.0 Conclusion

From the foregoing, it will be appreciated that specific embodiments ofthe disclosed technology have been described herein for purposes ofillustration, but that various modifications may be made withoutdeviating from the technology. For example, therapy signals describedherein can be delivered at combinations of parameter values within theforegoing ranges at values that are not expressly disclosed herein.Certain aspects of the technology described in the context of particularembodiments may be combined or eliminated in other embodiments. Forexample, the therapy signal can be monophasic with a passive chargeelimination phase. In some embodiments, the foregoing techniques can beused to address patient deficits than pain. Further, while advantagesassociated with certain embodiments of the disclosed technology havebeen described in the context of those embodiments, other embodimentsmay also exhibit such advantages, and not all embodiments neednecessarily exhibit such advantages to fall within the scope of thepresent technology. Accordingly, the disclosure and associatedtechnology can encompass other embodiments not expressly shown ordescribed herein.

The use of “and/or” in reference to a list of two or more items is to beinterpreted as including (a) any single item in the list, (b) all of theitems in the list, or (c) any combination of the items in the list.Additionally, the term “comprising” is used throughout to mean includingat least the recited feature(s) such that any greater number of the samefeature and/or additional types of other features are not precluded. Itwill also be appreciated that specific embodiments have been describedherein for purposes of illustration, but that various modifications maybe made without deviating from the technology. Further, while advantagesassociated with certain embodiments of the technology have beendescribed in the context of those embodiments, other embodiments mayalso exhibit such advantages, and not all embodiments need necessarilyexhibit such advantages to fall within the scope of the technology.Accordingly, the disclosure and associated technology can encompassother embodiments not expressly shown or described herein.

Where a range of values is provided, it is understood that eachintervening value, to the tenth of the unit of the lower limit unlessthe context clearly dictates otherwise, to between the upper and lowerlimits of that range is also specifically disclosed. Each smaller rangebetween any stated value or intervening value in a stated range and anyother stated or intervening value in that stated range is encompassedwithin the disclosure. The upper and lower limits of these smallerranges may independently be included or excluded in the range, and eachrange where either, neither or both limits are included in the smallerranges is also encompassed within the disclosure, subject to anyspecifically excluded limit in the stated range. Where the stated rangeincludes one or both of the limits, ranges excluding either or both ofthose included limits are also included in the disclosure.

1. A patient treatment system, comprising: a signal generator having acomputer readable storage medium with instructions that, in operation,generate a therapy signal having a base component and a high frequencycomponent, wherein— the base component has pulses with a non-zeroamplitude and a pulse width in a pulse width range of from about 5 ms toabout 2 seconds, and the high frequency component includes highfrequency pulses having a frequency in a frequency range of from about1.2 kHz and about 100 kHz, wherein the high frequency pulses have anorigin at the non-zero amplitude of the base component; and a signaldelivery element coupleable to the signal generator, wherein the signaldelivery element is positionable proximate a spinal cord region, and, inoperation, delivers the therapy signal to the spinal cord region.
 2. Thepatient treatment system of claim 1 wherein the pulse width of the basecomponent pulses is in a pulse width range of from about 5 ms to about100 ms.
 3. The patient treatment system of claim 1 wherein the pulsewidth of the base component pulses is in a pulse width range of fromabout 50 ms to about 2 seconds.
 4. The patient treatment system of claim1 wherein the pulse width of the base component pulses is in a pulsewidth range of from about 100 ms to about 2 seconds.
 5. The patienttreatment system of claim 1 wherein the pulse width of the basecomponent pulses is in a pulse width range of from about 500 ms to about2 seconds.
 6. The patient treatment system of claim 1 wherein the highfrequency pulses have an amplitude greater than the non-zero amplitudeof the base component pulses.
 7. The patient treatment system of claim 1wherein the high frequency pulses have a frequency of 10 kHz.
 8. Thepatient treatment system of claim 1 wherein the high frequency pulseshave a pulse width in a pulse width range of between about 10microseconds and about 333 microseconds.
 9. The patient treatment systemof claim 1 wherein the high frequency pulses include bursts of highfrequency pulses, wherein adjacent bursts of high frequency pulses areseparated by a quiescent interval during which no high frequency pulsesare delivered.
 10. The patient treatment system of claim 1 wherein thebase component pulses include a plurality of biphasic pulses having ananodic pulse phase and a cathodic pulse phase, and wherein at least oneof the anodic pulse phase or the cathodic pulse phase has the pulsewidth in the pulse width range from about 5 ms to about 2 seconds. 11.The patient treatment system of claim 10 wherein the high frequencypulses occur during the anodic pulse phase and/or the cathodic pulsephase.
 12. The patient treatment system of claim 10 wherein the basecomponent pulses include an interphase interval between the anodic pulsephase and the cathodic pulse phase, and wherein the high frequencypulses do not occur during the interphase interval.
 13. The patienttreatment system of claim 10 wherein adjacent bi-phasic pulses of theplurality of biphasic pulses of the base component pulses are separatedby an interpulse interval, and wherein the high frequency pulses do notoccur during the interpulse interval.
 14. The patient treatment systemof claim 10 wherein the high frequency pulses include bursts of highfrequency pulses, wherein adjacent bursts of high frequency pulses areseparated by a quiescent interval during which no high frequency pulsesare delivered.
 15. The patient treatment system of claim 14 wherein atleast two bursts of high frequency pulses occur during each anodic pulsephase and/or each cathodic pulse phase.
 16. The patient treatment systemof claim 1 wherein the base component pulses include a plurality ofmonophasic pulses having the non-zero amplitude.
 17. The patienttreatment system of claim 1 wherein the therapy signal at leastpartially suppresses at least a subset of neurons in the spinal cordregion.
 18. The patient treatment system of claim 17 wherein the subsetof neurons includes WDR neurons.
 19. The patient treatment system ofclaim 17 wherein the subset of neurons includes NS neurons.
 20. Thepatient treatment system of claim 17 wherein the subset of neuronsincludes both WDR neurons and NS neurons.
 21. The patient treatmentsystem of claim 1 wherein the signal delivery element includes anelectrode, and wherein the non-zero amplitude of the base componentpulses is selected to be at or below a maximum amplitude of the therapysignal that the electrode can tolerate based at least in part on thepulse width, the electrode material, and/or the surface area of theelectrode.
 22. A method for treating a patient, comprising: programminga signal generator to deliver a therapy signal to a target neuralpopulation in the patient's spinal cord region via at least oneimplanted signal delivery element, wherein the therapy signal includes(i) a base component having pulses with a non-zero amplitude and a pulsewidth in a pulse width range of from about 5 ms to about 2 seconds, and(ii) a high frequency component including high frequency pulses having afrequency in a frequency range of from about 1.2 kHz and about 100 kHz,wherein the high frequency pulses have an origin at the non-zeroamplitude of the base component. 23-42. (canceled)
 43. A method fortreating a patient, comprising: applying a therapy signal to the patientvia a treatment system, wherein the treatment system includes a signaldelivery element positioned proximate a spinal cord region of thepatient, and wherein the therapy signal includes (i) a base componenthaving pulses with a non-zero amplitude and a pulse width in a pulsewidth range of from about 5 ms to about 2 seconds, and (ii) a highfrequency component including high frequency pulses having a frequencyin a frequency range of from about 1.2 kHz and about 100 kHz, whereinthe high frequency pulses have an origin at the non-zero amplitude ofthe base component. 44-68. (canceled)